Escherichia coli (E. coli) is a common species of bacteria that is notorious for, among other things, causing intestinal problems including diarrhea. One class of E. coli that is associated with intestinal disease and/or diarrhea is the so-called enterotoxigenic E. coli (ETEC). ETEC are probably best known for causing traveler's diarrhea. Contamination of the food and/or water supply are typically the source of ETEC.
The disease caused by ETEC is the result of both the adhesion of the bacteria to the intestinal wall and the release of toxins (e.g., enterotoxins) into the system of the host. Adhesion to the intestinal wall is accomplished through one or more “fimbriae” (i.e., appendages) that are disposed on the exterior of the bacteria and allow it adhere. The fimbriae of a particular ETEC strain tend to be host-specific. For example, the ETEC that infect pigs carry K-88 fimbriae whereas strains that infect humans carry CFA I and CFA II fimbriae.
ETEC produce two toxins: the heat-labile “LT” toxin and the heat-stable “ST” toxin. The LT toxin includes an active or “A” subunit and five binding or “B” subunits. LT acts in a manner similar to cholera toxin in that it increases the level of cAMP in intestinal cells, and this causes an increase in electrolyte and water excretion (diarrhea). The ST toxin may be “type a” (i.e., STa) or “type b” (i.e., STb). ST stimulates production of cGMP, also leading to increased fluid excretion and diarrhea. Because enterotoxigenic E. coli strains are non-invasive, they do not cause inflammation, bloody diarrhea, or systemic symptoms such as fever.
In the North American (and World-Wide) swine industry, neonatal and post-weaning diarrhea caused by ETEC is one of the most economically important porcine diseases. For example, ETEC strains are believed to be responsible for the death of 10.8% of all pre-weaned pigs and up to more than 3% of all weaned pigs. (Tubb et al., 1993, Preweaning morbidity and mortality in the United States swine heed, Swine Health Prod. 1:21-28; Hampson, 1994, Postweaning Escherichia coli diarrhea in pigs, pp 171-191 in ed. C. L. Gyle, Escherichia coli in domestic animals and humans, CAB International, Oxon, UK; Dewey et al., 2000, The impact of disease on nursery pig production, Amer. Assoc. Swine Practictionsers, P 3-11, Indianapolis; the entire disclosures of which are all incorporated herein by reference). There is an ongoing need for ways to treat and/or prevent neonatal and post-weaning diarrhea in pigs.